Staphylococcus infections have since long been a widely spread problem around the world, which also gradually has been aggravated due to development of resistance against different antibiotic medicaments used for treatment of Staphylococcus infections.
Staphylococci are spherically formed Gram-positive bacteria that are common in our daily environment. Under a microscope they appear round and form in grape-like clusters. The Staphylococcus genus includes more than thirty species, e.g. Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus. Staphylococcus aureus belongs to the normal human bacterial flora and is present on the skin, on mucous membranes, and in the nostrils (nares). Staphylococcus epidermidis is present on the skin, in the nostrils, and in the oral cavity, while Staphylococcus saprophyticus is present in the urinary tract.
Staphylococcal enterotoxins produced when these strains are allowed to grow in improperly stored food are a common cause of food poisoning leading to vomiting and diarrhoea.
Staphylococcus epidermidis is mostly present on the skin of humans and may induce infections with pus formation under the skin, in particular for persons with reduced immune resistance. These strains may also give rise to sepsis, in particular for severely diseased patients, e.g. having long term intravenous catheters.
Staphylococcus saprophyticus rarely induces diseases, but may in certain situations give rise to urinary tract infections.
In particular, Staphylococcus aureus gives rise to a wide variety of diseases in humans and animals through either toxin production or invasion. Staphylococcus aureus, S. aureus for short, also known as golden staph, is the most common cause of Staphylococcus infections, and can cause a range of illnesses from minor skin infections, such as pimples, impetigo, boils, cellulitis folliculitis, furuncles, carbuncles, scalded skin syndrome and abscesses, to life-threatening diseases, such as pneumonia, meningitis, osteomyelitis endocarditis, toxic shock syndrome (TSS), and septicemia. Its incidence is from skin, soft tissue, respiratory, bone, joint, and endovascular to wound infections. It is still one of the four most common causes of nosocomial infections, often causing post-surgical wound infections.
S. aureus may occur as a commensal on human skin, and in about a third of the population, it frequently also occurs in the nose, but in the throat less commonly. The occurrence of S. aureus under these circumstances does not always indicate infection and therefore does not always require treatment. It can survive on domesticated animals such as dogs, cats, pigs and horses. It can survive for some hours on dry environmental surfaces. S. aureus can infect other tissues when the normal barriers have been breached, e.g. skin or mucosal lining. This leads to furuncles (boils) and carbuncles (a collection of furuncles). In infants S. aureus infection can cause a severe disease called Staphylococcal scalded skin syndrome (SSSS). S. aureus infections can be spread through contact with pus from an infected wound, skin-to-skin contact with an infected person by producing hyaluronidase that destroy tissues, and contact with objects such as towels, sheets, clothing, or athletic equipment used by an infected person. Deeply situated S. aureus infections can be very severe. Prosthetic joints put a person at particular risk for septic arthritis, and staphylococcal endocarditis (infection of the heart valves) and pneumonia, which may be rapidly spread. S. aureus is extremely prevalent in atopic dermatitis patients, who are less resistant to it than other people. It often causes complications. The disease is most likely found in fertile active places of the human body, as well as the armpits, the hair and the scalp. Large pimples in those areas will, when popped, cause the worst of the infection. Some strains of S. aureus produce toxic shock syndrome toxin, which is the causative agent for toxic shock syndrome. Some S. aureus strains that produce an enterotoxin are the cause ofstaphylococcal food poisoning, as also mentioned above. Further, S. aureus is one of the causal agents of mastitis in dairy cows.
Staphylococcus strains have an extraordinary ability to develop resistance against antibiotics. Staphylococcal resistance to penicillin is mediated by penicillinase (a form of β-lactamase) production: an enzyme which breaks down the β-lactam ring of the penicillin molecule. Penicillinase-resistant penicillins such as methicillin, oxacillin, cloxacillin, dicloxacillin, and nafcillin, are able to resist degradation by staphylococcal penicillinase.
Today, S. aureus has become resistant to many commonly used antibiotics. In the UK, only 2% of all S. aureus isolates are sensitive to penicillin with a similar picture in the rest of the world, due to a penicillinase, which is a form of β-lactamase. The β-lactamase-resistant penicillins (methicillin, oxacillin, cloxacillin and flucloxacillin) were developed to treat penicillin-resistant S. aureus and are still used as first-line treatment. Methicillin was the first antibiotic in this class to be used. It was introduced in 1959, but only two years later the first case of methicillin-resistant S. aureus (in the following called MRSA for short) was reported in England.
Despite this, MRSA generally remained an uncommon finding even in hospital settings until the 1990s when there was an explosion in MRSA prevalence in hospitals, where it now is endemic.
MRSA infections in both the hospital and community setting are commonly treated with non-β-lactam antibiotics such as clindamycin (a lincosamine) and co-trimoxazole (also commonly known as trimethoprim/-sulfamethoxazole). Resistance to these antibiotics has also led to the use of new, broad-spectrum anti-Gram positive antibiotics such as linezolid because of its availability as an oral drug. First-line treatment for serious invasive infections due to MRSA currently include glycopeptide antibiotics (vancomycin and teicoplanin). There are a number of problems with these antibiotics, mainly centred around the need for intravenous administration (there is no oral preparation available), toxicity, and the need to regularly monitor drug levels by means of blood tests. There are also concerns that glycopeptide antibiotics do not penetrate very well into infected tissues. This is a particular concern with infections of the brain and meninges, and in endocarditis. Glycopeptides must not be used to treat methicillin-sensitive S. aureus as outcomes are inferior.
Because of the high level of resistance to penicillins, and because of the potential for MRSA to develop resistance to vancomycin, the Centers for Disease Control and Prevention have published guidelines for the appropriate use of vancomycin. In situations where the incidence of MRSA infections is known to be high, the attending physician may choose to use a glycopeptide antibiotic until the identity of the infecting organism is known. When the infection is confirmed to be due to a methicillin-susceptible strain of S. aureus, then treatment can be changed to flucloxacillin or even penicillin as appropriate. However, several newly discovered strains of MRSA show antibiotic resistance even to vancomycin and teicoplanin.
Vancomycin-resistant S. aureus (VRSA) is a strain of S. aureus that has become resistant to the glycopeptides. The first case of vancomycin-intermediate S. aureus (VISA) was reported in Japan in 1996, but the first case of S. aureus truly resistant to glycopeptide antibiotics was only reported in 2002. Three cases of VRSA infection have been reported in the United States as of 2005.
Staphylococcus infections, including MRSA, occur most frequently among the persons in hospitals and health care facilities. MRSA infections that occur in otherwise healthy people who have not been recently hospitalized or have not undergone any medical procedure are known as community-associated (CA)-MRSA-infections. The colonisation of MRSA can be long-resting, sometimes over years.
MRSA may colonize at different locations in the human body, such as in the ear, the nasal and the pharyngeal region, in the gastro-intestinal region, in the urine, and on the skin. Examples of skin infections are boils, abscesses, styes (infection of glands in the eyelid), carbuncles, cellulites, and impetigo. If colonized in the blood or in other organs or parts within the body, an infection occurs, e.g. septicaemia (blood poisoning), septic shock, septic arthritis, osteomyelitis, internal abscesses, meningitis, pneumonia, and endocarditis. Long-term carriers have a higher risk of infection and may also spread the MRSA to other people.
Prophylaxis against Staphylococcus infections is difficult, and vaccination is not a very effective way. Persons showing antibiotic resistance against Staphylococcus strains are normally isolated at an infection clinic or corresponding institute with a view to avoiding spread of infection. Thus, in particular MRSA has become a major problem in hospitals in many countries and the spread of MRSA has to be prevented.
As appears above, the treatment of MRSA depends on whether a person is infected with Staphylococcus aureus or only colonised. Most MRSA infections will require treatment in hospital and antibiotic treatment may need to continue for several weeks. If a person is colonised with MRSA and need to go into hospital for an operation, he requires treatment to remove the MRSA, e.g. with a special antibiotic cream on the skin or inside the nose to remove the bacteria. It may also be necessary to wash the skin and hair with an antiseptic shampoo and lotion. In the hospital a private room is also needed to stop MRSA spreading.
As appears above, there is a need of an improved treatment, and also prophylaxis, of Staphylococcus induced infections and also to prevent further spreading of Staphylococci from an individual carrying Staphylococci, regarless whether an infection has been developed or not, in particular in view of resistant Staphylococcus strains.